The presence of chronic arterial inflammation in response to atherogenic stimuli has become a central tenet in explaining the development and destabilization of atherosclerotic plaques. Oxidized lipids play a central role in mediating a variety of immune, pro-inflammatory and plaque destabilizing processes that further amplify the inflammatory response. Underlying this inflammatory cascade is the production and secretion of cytokines, growth factors and metalloproteinases, such as interleukin-1 (IL-1), tumor necrosis factor alpha and C-reactive protein (CRP). Genetic variations in the IL-1 gene family (chromosome 2q13 region) commonly found in the human population can affect pro-inflammatory gene regulation and have been associated with elevated levels of pro-inflammatory mediators and increased risk for early cardiovascular events.
Oxidized phospholipids (OxPL) are present in atherosclerotic but not normal arteries. Plasma levels of specific OxPL on apolipoprotein B-100 (apoB) particles (OxPL/apoB) can be measured with the murine monoclonal antibody E06. OxPL/apoB levels are elevated in patients with coronary, carotid and femoral artery disease, acute coronary syndromes, and following percutaneous coronary intervention. Interestingly, in human plasma, OxPL are preferentially carried by Lp(a) lipoprotein (a) [Lp(a)], compared to other apoB-100 particles. Methods for determining the “atherogenesis index” (AI) (e.g., determining the ratio of OxPL/apoB) are provided in U.S. patent application Ser. No. 11/244,300 (Pub. No. 20060177435), which is incorporated herein by reference in its entirety.